Adaptation of membrane-associated determinants is an outgrowth of their metabolism

Abstract

The quantity of receptors expressed by specialized cells for hormones, foreign antigenic substances, and other chemical stimuli diminishes after they associate with ligands, correlating with a specific reduction in the responsiveness of the cell to further stimulation. Ligand-induced adaptation of membrane receptors may be akin to antigenic modulation--the reversible disappearance of membrane-associated determinants stimulated by specific antibodies. Antigenic modulation has been studied extensively in the thymus-leukemia (TL) system of mouse leukemias. Antibody-induced changes in the quantities of TL antigens expressed by ASL-1 and RADA-1 cells, independently arising leukemia cell lines of strain A mice, are outgrowths of their metabolic turnover. After interacting with TL antibodies, the rate of TL antigen disappearance from the membrane increases while the rate of antigen synthesis remains unchanged. Antiserum with specificities for two membrane-associated determinants of ASL-1 cells, TL and a tumor-associated antigen, leads to modulation of TL antigens alone; the tumor antigen persists. Selectivity of modulation is taken as an indication that complex cellular controls govern the affect of antiserum on the expression of membrane antigens. To detect the presence of regulatory controls governing the expression of membrane determinants, stable somatic hybrids of ASL-1 murine leukemia cells and LM(TK)- cells, a sustained mouse cell line, were prepared and antiserum affects on membrane antigen expression were investigated. The metabolic half-lives of each of three antigen determinants investigated was distinct from the others examined. The hybrid cells have lost their capacity to mudulate TL antigens. TL antigens of hybrid cells, unlike those of parental ASL-1 cells, continue to be expressed in the presence of high titers of TL antiserum. Similarities between antigenic modulation and down regulation exist, among which are the fate of receptor-ligand complexes, changes in their metabolism after binding to ligand, and the dependence of the reactions upon continued sources of cellular energy.